Hemorrhagic complications are clinically apparent in 1% of all nursery admissions and major hemorrhage or thrombosis is present in 40% of neonatal deaths. Before accurate detection, treatment, and prevention of neonatal bleeding and thrombosis is possible; it is necessary to determine the normal development of fetal blood coagulation, the control mechanisms governing normal development, and the effects of stress, including fetal hypoxia and premature delivery, on the development of blood coagulation. The normal developmental patterns of blood coagulation in the fetus and the effects of fetal hypoxia and premature delivery during the last trimester of pregnancy will be investigated in a chronic fetal lamb preparation. With this preparation serial sampling of fetal blood for measurements of coagulation factor activities can be obtained during the last 45 to 50 days of the normal 150 day gestation in the sheep. Sampling from the fetus prior to and following fetal hypoxia and premature delivery will be done and results of coagulation factor activities in these samples compared with results obtained from fetal blood obtained during normal gestation. Cortisol and thyroxin will also be investigated relative to their role in controlling normal maturation by correlating the levels of these hormones with changes in coagulation factor activities, and by measuring the effects of exogenous administration of these hormones on coagulation factors in vivo and in vitro in the fetal lamb and fetal lamb liver. The development of blood coagulation in the fetal lamb is similar to that proposed for humans. Newborn lambs also develop diseases including the respiratory distress syndrome, CNS hemorrhage, and probably necrotizing enterocolitis; each of which has been associated with prematurity, fetal hypoxia, and abnormalities of coagulation in the human. Therefore study of the normal development of blood coagulation, its control and the effects of fetal hypoxia and premature delivery on fetal coagulation in the chronic fetal lamb model will provide information of sufficient relevance to suggest approaches to the detection, treatment, and perhaps prevention of bleeding in the human newborn.